de-Madaria Enrique, del Mar Francés María, Gea-Sorlí Sabrina, Gutiérrez Luis M, Viniegra Salvador, Pérez-Mateo Miguel, Closa Daniel, Lopez-Font Inmaculada
From the *Unidad de Gastroenterología, Hospital General Universitario de Alicante; †Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior Investigaciones Científicas, Alicante; ‡Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior Investigaciones Científicas, Insitut d'Investigacions Biomédiques August Pi i Sunyer, and Centro Investigación Biomédica en Red: Enfermedades Hepáticas y Digestivas, Barcelona; §Universidad Miguel Hernández, Elche; and ∥Centro Investigación Biomédica en Red: Enfermedades Neurodegenerativas, Madrid, Spain.
Pancreas. 2014 Aug;43(6):895-902. doi: 10.1097/MPA.0000000000000152.
The objective of this study was to evaluate whether an uncontrolled activation of mast cells and macrophages through protease-activated receptor-2 (PAR-2) during acute pancreatitis could develop lung injury.
Pancreatitis was induced in rats by intraductal infusion of sodium taurocholate. In a group of animals, PAR-2 antagonist or trypsin (TRP) inhibitor was intravenously administered before the pancreatitis induction. In additional groups, the animals were treated with PAR-2-activating peptide or pancreatic TRP. The myeloperoxidase (MPO) activity was measured to evaluate the progression of inflammation.
Plasma from the animals with pancreatitis and pancreatic TRP induced the secretion of mast cells and alveolar macrophages as well as increased the density of PAR-2 in the plasma membrane. The treatment of alveolar macrophages with TRP, tryptase, as well as PAR-1- and PAR-2-activating peptide led to an increase in calcium-triggered exocytosis. Similar results were obtained in acinar cells. The intravenous injection of PAR-2-activating peptide and TRP induced an increase in MPO activity in the lung. The intravenous injection of PAR-2 antagonist or TRP inhibitor before the pancreatitis induction could prevent the increase in MPO activity in the pancreas and the lung.
The TRP generated during acute pancreatitis could be involved in the progression of lung injury through the activation of PAR-2 in alveolar macrophages.
本研究的目的是评估急性胰腺炎期间通过蛋白酶激活受体-2（PAR-2）对肥大细胞和巨噬细胞的失控激活是否会导致肺损伤。
通过向大鼠胰管内注入牛磺胆酸钠诱导胰腺炎。在一组动物中，在诱导胰腺炎之前静脉注射PAR-2拮抗剂或胰蛋白酶（TRP）抑制剂。在其他组中，用PAR-2激活肽或胰腺TRP治疗动物。测量髓过氧化物酶（MPO）活性以评估炎症进展。
患有胰腺炎和胰腺TRP的动物的血浆诱导肥大细胞和肺泡巨噬细胞的分泌，并增加质膜中PAR-2的密度。用TRP、类胰蛋白酶以及PAR-1和PAR-2激活肽处理肺泡巨噬细胞导致钙触发的胞吐作用增加。在腺泡细胞中也获得了类似的结果。静脉注射PAR-2激活肽和TRP导致肺中MPO活性增加。在诱导胰腺炎之前静脉注射PAR-2拮抗剂或TRP抑制剂可以预防胰腺和肺中MPO活性的增加。
急性胰腺炎期间产生的TRP可能通过激活肺泡巨噬细胞中的PAR-2参与肺损伤的进展。
